The management of muscle-invasive bladder cancer (MIBC) is evolving with the introduction of more effective neoadjuvant and perioperative systemic therapies. As treatment responses improve, an increasing number of patients are considering whether radical cystectomy (RC) remains necessary, particularly when no residual tumour is detected after neoadjuvant treatment.
Although trimodality therapy is an established bladder-preserving option, the optimal management of patients who decline RC following neoadjuvant systemic therapy remains uncertain. Response-adapted strategies are being investigated, but accurately identifying patients who may safely avoid cystectomy remains a clinical challenge.
A new pooled analysis from San Raffaele Comprehensive Cancer Center examined outcomes among patients enrolled in prospective phase II trials who declined RC and underwent repeat transurethral resection of the bladder tumour (reTURBT). The study evaluated outcomes according to pathological response and explored whether baseline characteristics could help identify patients who might be considered for bladder-preserving approaches.
On October 22, 2026, the findings were published in ESMO Open under the title “Outcomes of patients with muscle-invasive bladder cancer who declined radical cystectomy in perioperative therapy trials conducted at San Raffaele Comprehensive Cancer Center.”
The study was authored by Chiara Mercinelli, Giuseppe Basile, Michela Piacentini, Antonio Cigliola, Brigida A. Maiorano, Debora Serafin, Emanuele Crupi, Gualtiero Guandalini, Giovanni L. Pastorino, Gaia Latini, Pietro Scilipoti, Giovanni Tremolada, Marco Moschini, Giorgio Brembilla, Francesco De Cobelli, Maurizio Colecchia, Alberto Briganti, Francesco Montorsi, and Andrea Necchi.
Study Design and Patient Population
This was a post-hoc pooled analysis of prospectively collected data from four investigator-initiated, single-arm phase II trials conducted at San Raffaele Comprehensive Cancer Center: PURE-01, SURE-01, SURE-02, and NureCombo.
The trials enrolled patients with cT2–4N0M0 MIBC and pure or predominant (≥50%) urothelial carcinoma. Patients who declined RC after neoadjuvant therapy underwent reTURBT, including resection of the previous tumour site and any visible residual lesions, with detrusor muscle sampling.
The bladder-preserving approach did not routinely include additional local treatment after reTURBT. Delayed cystectomy or chemoradiotherapy was used when residual disease or intravesical recurrence was identified. Adjuvant or maintenance systemic treatment continued according to the respective trial protocols.
Patients who declined RC underwent intensive surveillance, including cystoscopy every three months for the first two years and every six months thereafter, alongside scheduled imaging.
The main outcomes were event-free survival (EFS), metastasis-free survival (MFS), and overall survival (OS), all calculated from the initiation of neoadjuvant therapy. Exploratory analyses evaluated outcomes according to pathological response, baseline clinical T stage, histology, and treatment strategy.
Patient Characteristics and Treatment Outcomes
The analysis included 279 patients enrolled between February 2017 and July 2025. Of these, 213 (76.4%) underwent RC, 54 (19.3%) declined RC and underwent reTURBT, and 12 (4.3%) did not undergo surgical assessment. The reTURBT population differed from the cystectomy group. Patients undergoing reTURBT were more likely to have baseline cT2 disease (75.9% vs 44.1%) and more frequently received adjuvant or maintenance therapy (55.6% vs 20.2%).
Median follow-up was 57 months (IQR 29–77) in the overall population, but differed substantially between groups: 25 months (IQR 17–32) for reTURBT and 65 months (IQR 40–80) for RC. Among the 54 patients who underwent reTURBT, 11 (20.4%) subsequently received delayed cystectomy or chemoradiotherapy because of residual tumour and/or intravesical recurrence.
Of the 43 patients who received no further local treatment, 35 had no residual tumour, seven had residual disease, and one had unknown residual tumour status. Intravesical recurrence or disease progression occurred in three of seven patients (42.9%) with residual disease, compared with three of 35 (8.6%) without residual tumour.
One patient lacked pathological-stage information and was excluded from the outcome analyses, leaving 53 evaluable patients in the reTURBT group. Among these patients, 10 (18.9%) developed disease recurrence, including seven (13.2%) who developed distant metastases.
At 36 months, the estimated EFS was 66.7% (95% CI 54.5–81.7), MFS was 65.9% (95% CI 50.9–85.4), and OS was 82.7% (95% CI 72.4–94.6). In a sensitivity analysis counting delayed cystectomy or chemoradiotherapy as an event, 36-month bladder-intact EFS was 60.9% (95% CI 48.4–76.7).
Pathological Response and Survival Outcomes
One of the central findings concerned the relationship between pathological response and outcomes following neoadjuvant therapy. Complete response was defined as ypT0Nx in the reTURBT group, indicating no residual tumour detected at reTURBT without pathological lymph node assessment, and ypT0N0 in the RC group, confirming the absence of residual tumour and nodal involvement.
Among complete responders undergoing reTURBT, 24-month EFS was 87.6% (95% CI 76.9–99.7), MFS was 96.9% (95% CI 91.3–100), and OS was 96.7% (95% CI 91.2–100). Comparisons with complete responders undergoing RC did not identify statistically significant differences, with hazard ratios of 1.96 (95% CI 0.53–7.27) for EFS, 1.11 (95% CI 0.21–5.82) for MFS, and 0.90 (95% CI 0.10–8.40) for OS.
However, the findings were considerably less favourable among patients with residual disease. At 24 months, EFS was 19.3% versus 67.8%, MFS was 18.1% versus 67.8%, and OS was 50.4% versus 82.5% for non-complete responders undergoing reTURBT versus RC, respectively.
The overall comparisons across the four response-by-treatment groups were statistically significant for EFS, MFS, and OS (p<0.001 for all endpoints). These results highlight the prognostic importance of residual tumour following neoadjuvant therapy and the potential risks associated with avoiding definitive local treatment in patients without complete response.
Baseline Clinical Stage and Exploratory Subgroup Findings
The investigators also examined whether clinical characteristics were associated with outcomes following reTURBT compared with RC. Among patients with baseline cT3–4 disease, reTURBT was associated with significantly worse EFS than RC, with an age-adjusted HR of 2.34 (95% CI 1.05–5.22).
However, formal interaction testing did not demonstrate significant differences in treatment associations according to clinical stage, treatment strategy, or histology. No statistically significant OS differences between surgical approaches were identified within the examined subgroups.
The contribution of adjuvant or maintenance immune checkpoint inhibition remains uncertain, as no clear outcome differences were identified between perioperative and neoadjuvant-only treatment strategies. These exploratory findings suggest that baseline tumour extent may be relevant to patient selection, but they do not establish which patients can safely avoid cystectomy.
Clinical Implications and Study Limitations
The findings provide additional information for counselling patients with MIBC who consider bladder preservation after neoadjuvant systemic therapy. For patients without residual tumour detected at reTURBT, the favourable survival estimates support further prospective evaluation of response-adapted bladder-preserving strategies. However, the authors emphasised that clinical complete response requires careful assessment.
Bladder MRI may contribute to response evaluation, but imaging alone cannot reliably exclude residual tumour. The investigators highlighted the importance of combining radiological assessment, histological confirmation through reTURBT, and urinary cytology. Several limitations affect the interpretation of the results. This was a post-hoc, non-randomised analysis from a single specialised centre. Treatment groups differed in baseline characteristics, systemic treatment exposure, and follow-up duration.
The reTURBT population was relatively small, particularly among patients with residual disease, and shorter follow-up may have limited the detection of later recurrences. Delayed local treatments and potential guarantee-time bias further complicate comparisons between surgical approaches. Consequently, these findings should be regarded as hypothesis-generating rather than evidence that reTURBT provides equivalent outcomes to radical cystectomy.
Takeaway
This pooled post-hoc analysis of 279 patients with MIBC provides further evidence that pathological response following neoadjuvant therapy is strongly associated with subsequent clinical outcomes.
Patients with no residual tumour detected at reTURBT had favourable survival estimates, with 24-month MFS and OS exceeding 95%. In contrast, patients with residual disease who declined RC experienced substantially poorer outcomes than non-complete responders undergoing cystectomy.
The findings support further investigation of response-adapted bladder preservation in carefully selected patients while reinforcing the importance of definitive local treatment for those with residual high-grade disease.
Given the non-randomised design, small subgroups, and differences in follow-up, these results do not establish reTURBT as an equivalent alternative to radical cystectomy. Prospective validation remains necessary before such approaches can be incorporated into routine clinical practice.
The full article is available in ESMO Open.
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